{"gene":"PF3D7_0501700","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2018,"finding":"APC3 (PF3D7_0501700 ortholog in P. berghei) localizes as a single focus co-localizing with the centriolar plaque during asexual schizogony, and as multiple foci in male gametocytes, as determined by live-cell imaging and reverse genetics.","method":"Live-cell imaging and reverse genetics (gene disruption, conditional knockdown) in P. berghei","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence established by gene disruption and conditional knockdown in a single lab using two complementary genetic approaches","pmids":["29618731"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2018,"finding":"Gene disruption and conditional knockdown of APC3 in P. berghei revealed essential roles during mitotic stages: loss of APC3 results in lack of chromosome condensation, abnormal cytokinesis, and absence of microgamete formation, establishing APC3 as a key component of the APC/C E3 ubiquitin ligase required for atypical mitosis during male gametogenesis.","method":"Gene disruption and conditional knockdown with phenotypic readouts (chromosome condensation, cytokinesis, microgamete formation) in P. berghei","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — two orthogonal loss-of-function approaches (gene disruption + conditional knockdown) with clearly defined cellular phenotypes, replicated in body-mention citations across multiple subsequent papers","pmids":["29618731"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"In Plasmodium berghei, APC3 (PF3D7_0501700) is a subunit of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase that localizes to the centriolar plaque during asexual schizogony and is essential for chromosome condensation, cytokinesis, and microgamete formation during atypical closed endomitosis in male gametogenesis; its function during P. falciparum blood-stage schizogony remains uncharacterized."},"narrative":{"mechanistic_narrative":"APC3 (PF3D7_0501700) is a subunit of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase that governs the atypical, closed mitotic divisions of Plasmodium [PMID:29618731]. In P. berghei, APC3 localizes as a single focus coinciding with the centriolar plaque during asexual schizogony and resolves into multiple foci in male gametocytes, linking its distribution to the sites of spindle organization during proliferative stages [PMID:29618731]. Loss-of-function studies in P. berghei establish that APC3 is essential during mitosis: its disruption abolishes chromosome condensation, produces abnormal cytokinesis, and prevents microgamete formation during male gametogenesis [PMID:29618731]. All available mechanistic evidence derives from the P. berghei ortholog; the function of PF3D7_0501700 during P. falciparum blood-stage schizogony has not been characterized in the available corpus, and no direct biochemical demonstration of its E3 ligase activity, substrate targets, or interaction map is present.","teleology":[{"year":2018,"claim":"To place APC3 in the cell-division machinery, its subcellular distribution across proliferative stages was resolved, revealing an association with the centriolar plaque that ties it to the spindle-organizing center during closed mitosis.","evidence":"Live-cell imaging combined with reverse genetics (gene disruption and conditional knockdown) in P. berghei","pmids":["29618731"],"confidence":"Medium","gaps":["The molecular basis of centriolar-plaque recruitment is not defined","Localization was characterized in P. berghei only, not for P. falciparum PF3D7_0501700","No demonstration that the imaged foci represent an assembled, active APC/C complex"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2018,"claim":"To test whether APC3 is functionally required rather than merely present, orthogonal loss-of-function approaches defined discrete mitotic phenotypes, establishing APC3 as an essential APC/C component for chromosome condensation, cytokinesis, and microgametogenesis.","evidence":"Gene disruption plus conditional knockdown with phenotypic readouts (chromosome condensation, cytokinesis, microgamete formation) in P. berghei","pmids":["29618731"],"confidence":"High","gaps":["The ubiquitination substrates of the APC3-containing APC/C in Plasmodium are not identified","Direct E3 ligase activity and the composition of the APC/C complex are not biochemically reconstituted","Requirement during P. falciparum blood-stage schizogony is untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"Whether PF3D7_0501700 performs the same essential APC/C role during P. falciparum asexual and sexual development, and which cell-cycle substrates it targets for ubiquitination, remains unresolved.","evidence":"No direct experimental evidence in the available corpus addresses P. falciparum PF3D7_0501700 function or substrate identity","pmids":[],"confidence":"Low","gaps":["No functional characterization of PF3D7_0501700 in P. falciparum","No substrate or interaction data for the Plasmodium APC/C","No structural model of the APC3 subunit or complex"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Anaphase-promoting complex/cyclosome (APC/C)"],"partners":[],"other_free_text":["All functional and localization evidence derives from the P. berghei ortholog; PF3D7_0501700 function in P. falciparum is uncharacterized in the corpus.","APC3 localizes to a single centriolar-plaque focus during asexual schizogony and multiple foci in male gametocytes [#0].","Loss of APC3 abolishes chromosome condensation, disrupts cytokinesis, and prevents microgamete formation during male gametogenesis [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"29618731","id":"PMC_29618731","title":"Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29618731","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30127502","id":"PMC_30127502","title":"Author Correction: Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30127502","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41218080","id":"","title":"Plasmodium actin-like proteins are essential for DNA segregation during male gametogenesis and malaria transmission.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/41218080","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36862652","id":"","title":"Plasmodium schizogony, a chronology of the parasite's cell cycle in the blood stage.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/36862652","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38563493","id":"","title":"The molecular mechanisms driving Plasmodium cell division.","date":"2024","source":"Biochemical Society transactions","url":"https://pubmed.ncbi.nlm.nih.gov/38563493","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37630530","id":"","title":"Plasmodium falciparum Development from Gametocyte to Oocyst: Insight from Functional Studies.","date":"2023","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/37630530","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39207167","id":"","title":"A multistage Plasmodium CRL4WIG1 ubiquitin ligase is critical for the formation of functional microtubule organization centers in microgametocytes.","date":"2024","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/39207167","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39255311","id":"","title":"Plasmodium NEK1 coordinates MTOC organisation and kinetochore attachment during rapid mitosis in male gamete formation.","date":"2024","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/39255311","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36898988","id":"","title":"The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/36898988","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35782151","id":"","title":"Gametogenesis in Plasmodium: Delving Deeper to Connect the Dots.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35782151","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38416790","id":"","title":"Plasmodium falciparum contains functional SCF and CRL4 ubiquitin E3 ligases, and CRL4 is critical for cell division and membrane integrity.","date":"2024","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38416790","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31824870","id":"","title":"Who Needs a Contractile Actomyosin Ring? The Plethora of Alternative Ways to Divide a Protozoan Parasite.","date":"2019","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31824870","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["APC3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13888,"output_tokens":662,"usd":0.025797,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5287,"output_tokens":1709,"usd":0.03458,"stage2_stop_reason":"end_turn"},"total_usd":0.060377,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"APC3 (PF3D7_0501700 ortholog in P. berghei) localizes as a single focus co-localizing with the centriolar plaque during asexual schizogony, and as multiple foci in male gametocytes, as determined by live-cell imaging and reverse genetics.\",\n      \"method\": \"Live-cell imaging and reverse genetics (gene disruption, conditional knockdown) in P. berghei\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence established by gene disruption and conditional knockdown in a single lab using two complementary genetic approaches\",\n      \"pmids\": [\"29618731\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Gene disruption and conditional knockdown of APC3 in P. berghei revealed essential roles during mitotic stages: loss of APC3 results in lack of chromosome condensation, abnormal cytokinesis, and absence of microgamete formation, establishing APC3 as a key component of the APC/C E3 ubiquitin ligase required for atypical mitosis during male gametogenesis.\",\n      \"method\": \"Gene disruption and conditional knockdown with phenotypic readouts (chromosome condensation, cytokinesis, microgamete formation) in P. berghei\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two orthogonal loss-of-function approaches (gene disruption + conditional knockdown) with clearly defined cellular phenotypes, replicated in body-mention citations across multiple subsequent papers\",\n      \"pmids\": [\"29618731\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"In Plasmodium berghei, APC3 (PF3D7_0501700) is a subunit of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase that localizes to the centriolar plaque during asexual schizogony and is essential for chromosome condensation, cytokinesis, and microgamete formation during atypical closed endomitosis in male gametogenesis; its function during P. falciparum blood-stage schizogony remains uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"APC3 (PF3D7_0501700) is a subunit of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase that governs the atypical, closed mitotic divisions of Plasmodium [#1]. In P. berghei, APC3 localizes as a single focus coinciding with the centriolar plaque during asexual schizogony and resolves into multiple foci in male gametocytes, linking its distribution to the sites of spindle organization during proliferative stages [#0]. Loss-of-function studies in P. berghei establish that APC3 is essential during mitosis: its disruption abolishes chromosome condensation, produces abnormal cytokinesis, and prevents microgamete formation during male gametogenesis [#1]. All available mechanistic evidence derives from the P. berghei ortholog; the function of PF3D7_0501700 during P. falciparum blood-stage schizogony has not been characterized in the available corpus, and no direct biochemical demonstration of its E3 ligase activity, substrate targets, or interaction map is present.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"To place APC3 in the cell-division machinery, its subcellular distribution across proliferative stages was resolved, revealing an association with the centriolar plaque that ties it to the spindle-organizing center during closed mitosis.\",\n      \"evidence\": \"Live-cell imaging combined with reverse genetics (gene disruption and conditional knockdown) in P. berghei\",\n      \"pmids\": [\"29618731\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular basis of centriolar-plaque recruitment is not defined\",\n        \"Localization was characterized in P. berghei only, not for P. falciparum PF3D7_0501700\",\n        \"No demonstration that the imaged foci represent an assembled, active APC/C complex\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To test whether APC3 is functionally required rather than merely present, orthogonal loss-of-function approaches defined discrete mitotic phenotypes, establishing APC3 as an essential APC/C component for chromosome condensation, cytokinesis, and microgametogenesis.\",\n      \"evidence\": \"Gene disruption plus conditional knockdown with phenotypic readouts (chromosome condensation, cytokinesis, microgamete formation) in P. berghei\",\n      \"pmids\": [\"29618731\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The ubiquitination substrates of the APC3-containing APC/C in Plasmodium are not identified\",\n        \"Direct E3 ligase activity and the composition of the APC/C complex are not biochemically reconstituted\",\n        \"Requirement during P. falciparum blood-stage schizogony is untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0501700 performs the same essential APC/C role during P. falciparum asexual and sexual development, and which cell-cycle substrates it targets for ubiquitination, remains unresolved.\",\n      \"evidence\": \"No direct experimental evidence in the available corpus addresses P. falciparum PF3D7_0501700 function or substrate identity\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional characterization of PF3D7_0501700 in P. falciparum\",\n        \"No substrate or interaction data for the Plasmodium APC/C\",\n        \"No structural model of the APC3 subunit or complex\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0061630\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0031145\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0007067\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"Anaphase-promoting complex/cyclosome (APC/C)\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"All functional and localization evidence derives from the P. berghei ortholog; PF3D7_0501700 function in P. falciparum is uncharacterized in the corpus.\",\n      \"APC3 localizes to a single centriolar-plaque focus during asexual schizogony and multiple foci in male gametocytes [#0].\",\n      \"Loss of APC3 abolishes chromosome condensation, disrupts cytokinesis, and prevents microgamete formation during male gametogenesis [#1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0501700","name":null,"product":"anaphase-promoting complex subunit 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1101500","name":null,"product":"anaphase-promoting complex subunit 3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1032200","name":null,"product":"anaphase-promoting complex subunit 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"APC3","evaluation":null}